Table 2.
Selected phase II/III studies with PARP inhibitors in gBRCA1/2m locally advanced and metastatic breast cancer
| Study | Disease | Phase | N | Treatment | Efficacy in patients with gBRCA1/2m |
|---|---|---|---|---|---|
| NCT0049423457 | Recurrent, advanced BC with median 3 prior regimens and BRCA1/2 mutation (BRCA1/2m) | II | 27 | Olaparib 400 mg BID | ORR: 41% (11/27) |
| OlympiAD NCT0200062261 | Metastatic BC with gBRCA1/2m | III | 302 | Olaparib 300 mg BID vs treatment of physician’s choice (TPC; capecitabine, eribulin, or vinorelbine) |
ORR: 60% with olaparib vs 29% with TPC PFS: 7.0 months with olaparib vs 4.2 months with TPC (hazard ratio 0.58; 95% CI: 0.43–0.80; P < 0.001) DoR: 6.4 months with olaparib (IQR, 2.8–9.7) vs 7.1 months with TPC (IQR, 3.2–12.2) |
| ABRAZO NCT0203491665 | Advanced BC with gBRCA1/2m following platinum or multiple cytotoxic regimens | II | 84 | Talazoparib 1 mg/day following platinum-based therapy (cohort 1) vs ≥3 platinum-free cytotoxic-based regimens (cohort 2) |
ORR: 21% (95% CI: 10–35) in cohort 1 vs 37% (95% CI: 21–55) in cohort 2 PFS: 4.0 months (95% CI: 2.8–5.4) in cohort 1 vs 5.6 months (95% CI: 5.5–7.8) in cohort 2 DoR: 5.8 months (95% CI: 2.8–NR) in cohort 1 vs 3.8 months (95% CI: 2.8–10.1) in cohort 2 CBR: 38% (95% CI: 24–53) in cohort 1 vs 66% (95% CI: 48–81) in cohort 2 |
| EMBRACA NCT0194577564 | Advanced BC with gBRCA1/2m | III | 431 | Talazoparib 1 mg/day vs physician’s choice of chemotherapy (PCT; capecitabine, eribulin, gemcitabine, or vinorelbine) |
ORR: 63% (95% CI: 56–69) with talazoparib vs 27% (95% CI: 19–36) with PCT PFS: 8.6 months (95% CI: 7.2–9.3) with talazoparib vs 5.6 (95% CI: 4.2–6.7) with PCT DoR: 5.4 months (95% CI: 2.8–11.2) with talazoparib vs 3.1 (95% CI: 2.4–6.7) with PCT CBR24: 69% (95% CI: 63–74%) with talazoparib vs 36% (95% CI: 28–45) |
| BRAVO NCT0190559266 | Metastatic BC with gBRCA1/2m (and HER2-negative) | III | 306 (est) | Niraparib vs physician’s choice of chemotherapy | ONGOING |
| Cancer Research UK67 | Previously treated advanced OC or BC with gBRCA1/2m | II |
78 n = 23 (BC) |
Rucaparib | 39% of BC patients (9/23) achieved stable disease ≥12 weeks |
| RUBY NCT0250504868 | HER2-negative metastatic BC associated with BRCAness phenotype determined by “high-tumour genomic LOH” score and/or a somatic BRCAm | II | 41 (est) | Rucaparib | ONGOING |
| Brocade 2 NCT0150660982 | Locally recurrent or metastatic BC with gBRCA1/2m | II | 284 | Paclitaxel/carboplatin/veliparib (PCV) vs paclitaxel/carboplatin/placebo (PCP) |
PFS: 14.1 months with PCV vs 12.3 months with PCP; hazard ratio 0.789 (95% CI: 0.536–1.162); P = 0.227 ORR: 78% with PCV vs 61% with PCP; P = 0.027 |
| Brocade 3 NCT0216369483 | Locally advanced or metastatic gBRCA1/2m BC (and HER2-negative) | III | 500 (est) | Paclitaxel/carboplatin/veliparib vs paclitaxel/carboplatin/placebo | ONGOING |
BC breast cancer, BID twice daily, CBR clinical benefit rate, CBR24 CBR at 24 weeks, CI confidence interval, DoR duration of response, est estimated, IQR interquartile range, LOH loss-of-heterozygosity, gBRCA1/2m germline BRCA1/2 mutation, OC ovarian cancer, ORR objective response rate, PARP poly(ADP-ribose) polymerase, PCP paclitaxel/carboplatin/placebo, PCV paclitaxel/carboplatin/veliparib, PCT physician’s choice chemotherapy, PFS progression-free survival, TNBC triple-negative breast cancer, TPC treatment of physician’s choice